Project Summary The past decade has witnessed remarkable progress in the scale-up of antiretroviral therapy (ART), yet access to optimal diagnosis, care, and treatment remains limited for many of the 2.1 million children living with perinatally-acquired HIV worldwide. Novel diagnostic technologies and antiretroviral drugs (ARVs) can address this treatment gap. Critical questions remain, however, about the most effective way to utilize these innovations for children in settings with very limited resources. For example, how should programs best introduce new point-of-care assays for infant HIV diagnosis, and what are the most effective and cost-effective approaches to roll out pediatric dolutegravir and other emerging ARVs? Where long-term data are limited, or traditional clinical studies are not feasible, computer-based microsimulation modeling can use existing data to inform decisions about how to achieve the best outcomes for children with HIV under constrained healthcare budgets. With NICHD R01 support (2014-2019), we developed the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric microsimulation model and have informed guidelines and decisions from the World Health Organization (WHO), the President's Emergency Plan for AIDS Relief (PEPFAR), and country Ministries of Health (MOHs). In the first 4 years of the initial award cycle, we have used microsimulation and cost- effectiveness analysis methods to publish 17 papers related to pediatric HIV prevention, diagnosis, and treatment. We now propose to broaden the scope of this work, expanding a multidisciplinary team with diverse expertise in pediatric HIV care, research, clinical policy, and cost-effectiveness, and adding Zimbabwe to the original focus countries of Cte d'Ivoire and South Africa. This will allow us to compare findings across three PEPFAR settings that encompass a wide and representative range of pediatric HIV epidemiology, clinical practice, and healthcare costs. We will also develop new model-based methods, including location-optimization models and regression-based metamodels that can be used by local program planners to examine emerging care and treatment approaches across the spectrum of pediatric HIV care. We propose two new specific aims: 1. To project the optimal placement and value of innovative diagnostic technologies for pediatric HIV, including point-of-care assays for infant HIV diagnosis. 2. To evaluate the most effective and cost-effective ways to implement new ARV guidelines and introduce new ARV formulations for children, including the planned rollout of dolutegravir. The goal of this proposal is to help clinicians, program planners, and policymakers at MOHs, WHO, and PEPFAR identify the optimal use of scarce resources to improve long-term health for children with HIV. Continuation and expansion of support for the CEPAC-Pediatric modeling program will allow us to develop and disseminate novel modeling methods and address critical, context-specific questions about how to make the best use of innovative new technologies and treatments for millions of children affected by HIV worldwide.